Locally Advanced Hepatocellular Carcinoma
Conditions
Keywords
Nivolumab, Cabozantinib, Neoadjuvant, Immunotherapy, Liver Cancer, Borderline Resectable, Advance Resectable, Neoplasms, Hepatocellular Carcinoma, HCC, Resection
Brief summary
The proposed study is an open-label, single institution, single arm phase 1b study of neoadjuvant cabozantinib plus nivolumab in patients with locally advanced HCC.
Interventions
DRUGCabozantinib
Cabozantinib (40mg) will be taken by mouth daily for 8 weeks.
DRUGNivolumab
Nivolumab 240mg intravenously every 2 weeks (days 14, 28, 42, and 56 for a total of four doses), in combination with Cabozantinib 40mg by mouth daily for 8 weeks.
Sponsors
Exelixis
Bristol-Myers Squibb
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must have locally advanced/borderline resectable hepatocellular carcinoma. 2. Must have measurable disease. 3. Age ≥18 years. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 5. Patients must have adequate organ and marrow function defined by study-specified laboratory tests. 6. Patients must have adequate liver remnant and function. 7. Antiviral therapy per local standard of care for hepatitis B. 8. Woman of child bearing potential must have a negative pregnancy test. 9. Must use acceptable form of birth control while on study. 10. Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
1. Fibrolamellar carcinoma or mixed HCC. 2. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 6 months prior to trial registration. 3. Concomitant Anticoagulation therapy. 4. Any GI or pulmonary risks of bleeding. 5. History of HIV Infection. 6. Active co-infection with hepatitis B and hepatitis C. 7. Active co-infection with hepatitis B and hepatitis D. 8. Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy. 9. History of any autoimmune disease requiring systemic treatment within the past 2 years. Any patient bearing an allograft is not eligible. 10. Any additional malignancies with treatment or life-limiting cancers. Superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy would not exclude participation in this trial. 11. Uncontrolled intercurrent illness. 12. Corrected QT interval calculated by the Fridericia formula. 13. Uncontrolled high blood pressure. 14. Are pregnant or breastfeeding. 15. Any gastrointestinal (GI) disorders. 16. Any certain study-specified heart conditions 6 months prior to enrollment. 17. Major surgery within 2 months before enrollment. 18. Have any evidence of moderate or severe ascites. 19. Any untreated or incompletely treated varices with bleeding or high-risk bleeding. 20. Inability to swallow intact tablets. 21. Known or suspected hypersensitivity to study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of adverse events in participants of neoadjuvant cabozantinib plus nivolumab. | 4 years |
| Number of patients who complete pre-op treatment and proceed to surgery. | 4 years |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of participants who obtain a major pathologic responses (MPR) | 4 years |
| Objective response rate (ORR) | 4 years |
| Percentage of participants who obtain R0 resection. | 4 years |
| Disease free survival (DFS) | 5 years |
| Median Overall Survival (OS) | 5 years |
| Percentage of participants who obtain a pathologic complete response (CR). | 4 years |
Countries
United States
Outcome results
None listed